The aim of this Program Project is to identify the genes and pathways responsible for development of familial IgA nephropathy (IgAN). The approaches in the 3 Projects will refine the genetic location of the recently identified disease locus on chromosome 6q22-23 (IGAM1), evaluate the biosynthesis of IgA1 and its glycosylation in B lymphocytes, and assess the pathogenic role of cir5cuylating immune complexes with undergalactosylated IgA1. These studies require many patients with well- defined clinical phenotypes and appropriate family members and controls. Patients with familial or sporadic IgAN, Henoch-Schonlein purpura (HSP), family members, and non-IgAN disease- and healthy control subjects in a 7-stage catchment area will be enrolled. To provide clinical resources and statistical support for the 3 Projects, Core A will collect blood and urine samples (and residual renal tissue if biopsy done within 30 days), compile clinical and laboratory data in aq centralized database, and correlate laboratory and clinical data. The Specific Aims of Core A are: 1. Enroll 1515 subjects for the 3 Projects: 20 pedigrees with 50 familial IgAN/HSP patients and about 150 of their family members, 150 Caucasian sporadic IgAN patients and 375 of their family members, 50 HSP patients and 125 of their family members, 50 African-American IgAN patients and 200 of their family members, 65 non-IgAN disease- controls, and 200 Caucasian and 100 African-American healthy controls. 2. Establish and manage the computerized database for the entire Program Project: (a) compile the demographic, clinical, laboratory, histopathologic, and genetic data; (b) coordinate and manage statistical analyses to ensure investigators have ready access to statistical consultation and support; (c) provide statistical expertise including sample-size estimation and power calculations, randomization procedures, and design of data collection forms; and (d) perform interim reviews and final analyses. 3. Coordinate collection and distribution of blood and urine samples from patients and controls, and establish immortalized cell lines from selected subjects. 4. Perform detailed histologic analyses of residual renal tissue of newly biopsied IgAN/HSP and non-IgAN glomerulonephritis patients from whom blood and urine samples will be obtained for contemporaneous in vitro studies. The findings from this Program Project will substantially increase the understanding of the pathogenesis of a common renal disease and may be the foundation for future development of a disease-specific therapy.